The carotid bodies are structures considered as chemoreceptors sensible to hypoxia. The morphological alterations that this organ shows after chronic hypoxia (high altitudes residents, chronic obstructive pulmonary disease  COPD) and arterial hypertension are well known. In these clinical situations there are also changes in the respiratory control, mainly the response to acute hypoxia. In this study we performed a quantitative analysis of the histology of carotid bodies collected from autopsies of 4 groups of patients: acute respiratory failure (acute respiratory distress syndrome  ARDS) (n = 7), systemic arterial hypertension (n = 7), COPD (n = 8) and controls (n = 9). Using morphometry, we measured the volume proportion of the 4 main histological cell subtypes found within the glomic tissue: light, dark, sustentacular and progenitor cells. We found a significant increase in the volume proportion of dark cells in the ARDS group when compared to the other groups (0.22 ± 0.05; 0.11 ± 0.04; 0.09 ± 0.03; 0.12 ± 0.05, respectively) (p < 0.0001). Patients with COPD showed a significant increase in sustentacular cells and reduced glomic tissue when compared to controls (p < 0.03). These results suggest that chronic and acute hypoxia have different effects on the histology of the glomic tissue. These findings are compatible with an acute response of the carotid bodies to hypoxia and indicate the necessity of functional studies of respiratory control in patients surviving ARDS.

PEEP and tidal volume titration, according to the pressure volume (P-V) curves improved survival in ARDS patients. There are several techniques described to study P-V curves, however, there are few studies comparing them. In order to determine the correlation between two different techniques of acquisition P-V curves we compared the lower (Lpflex) and upper inflection point (Upflex) of the static occlusion technique (SOC) versus the constant flow technique (CF) in 13 ARDS patients (LIS > 2.5). Volume variation was monitored by an inductive body an inductive body plethysmograph and by a flow transducer. Random VTs were tested after a fixed lung volume history. End inspiratory pressure after a 2s pause was recorded. CF was performed with a 1 L/min flow after a 40 cmH2O CPAP maneuver followed by disconnection. To prevent bias, a mathematical algorithm was used for Pflex calculation. A regression line of points corresponding to the 80% of maximal slope segment (Slopemax) was calculated. Regression lines of the points below and above Slopemax were also calculated. LPflex and UPflex were identified as the intersection of the regression lines. Results: LPflex and UPflex could be identified in all patients in the CF technique, while LPflex was identified in 12 patients, and UPflex in only 9 patients in the SOC technique. LPflex and UPflex are higher in the CF technique (LPflex was 16.0 ± 1.4 and 13.6 ± 1.5; UPflex was 33.1 ± 1.6 and 27.6 ± 1.6, respectively for CF and SOC). The track of SOC P-V curves is shifted to the left when compared with CF. Conclusion: Pflex could be identified in the majority of the patients. The difference observed between the two methods could be attributed to different lung time history and recruitment during SOC procedure.

Increased "lung tissue resistance" or viscoelastic pressure dissipation in patients with ARDS has been well documented. We suspected that part of this altered viscoelastic behavior could be caused by tidal recruitment (accommodation of tidal volume into new units). The purpose of this study is to analyze the viscoelastic dissipation of pressures across the respiratory system at progressive lung recruitment/de-recruitment conditions. We studied six ARDS patients, (< 5 days of evolution, LIS > 2.5). Incremental and decremental PEEP steps (2 cmH2O up to PPLAT 55 cmH2O, VT = 4 mL/kg, inspiratory pause = 2s), were subsequently applied and P (P = plateau pressure subtracted from pressure at zero flow) was calculated at each PEEP level. Lung volume changes were monitored with a body plethysmograph. Results: besides the non-linearity of pressure dissipations along different PEEP levels (fig. 1) a significant difference of P between the incremental and decremental PEEP steps was also observed (p < 0.0001). Conclusions: 1) A linear model describing the non Newtonian component of lung tissue resistance is not valid. 2) P is strongly influenced by lung recruitment. 3) "Classic" stress relaxation and stress recovery may depend on major changes of lung surface area during inspiratory pause.

The titration of the ideal PEEP by the lower inflection point of the PxV curve of the respiratory system (L-Pflex) associated with low tidal ventilation led to an improvement in survival in ARDS patients. Among the possible techniques to obtain the PxV curve at the beside the low constant flow (CF) is the easiest and quickest one. In order to evaluate the influence of 4 different CF (1, 2, 5 and 10 L/min) in the determination of L-Pflex and in inspiratory work (Wi-LxcmH2O  till 1.35 L above the FRC) we studied 7 ARDS patients (LIS > 2.5, < 5 days of evolution). After a CPAP maneuver of 40 cmH2O per 15s and 10s exhalation to atmosphere, the 7 patients randomly received the 4 inspiratory CF. We analyzed the PxV curve time, L-Pflex and Wi among the different flows, estimating the volume from the CF at ATPS (VCF) comparing with the measured volume by the respiratory inductive plethysmograph (RIP).

There was no difference of the L-Pflex or Wi among the different CFs comparing the estimated or measured volume. Conclusion: CF from 1 to 10 L/min can equally determine the L-Pflex in ARDS patients.

The correct adjust of PEEP and tidal volume (VT) can protect patients with ARDS from ventilator induced lung injury (VILI). "Best PEEP" could be set according to the best compliance, but this approach could be influenced by VT and lung recruitment. We studied 6 ARDS patients (mean LIS = 3,2) in order to determine the influence of VT and lung recruitment (at the PEEP level) on the static compliance (Cst, rs). We did a step-by-step ascending and descending maneuver with high (HVT) and low VT (LVT); 10 and 4 mL/kg, respectively. PEEP steps of 2 cmH2O was applied up to a PPLAT 55 cmH2O, and than it was removed. Volume variation was monitored with an inductive body plethysmograph. Respiratory work during ascending (W, rs, asc) and descending phases (W, rs, desc) were calculated on the area of the PEEP-end expiratory lung volume (EEL V) curve. Best PEEP was obtained from PEEP/Cst, rs curve W, rs, asc was higher than W, rs, desc (14.0 ± 1.1 versus 9.1 ± 1.5 L/cmH2O for LVT and 11.9 ± 0.8 versus 8.9 ± 1.1 L/cmH2O for HVT; p < 0.03 in both comparisons). The W, rs, asc of HVT was lower than the W, rs, asc of LVT (p < 0.05), but both W, rs, desc were not different. In spite of the lower W, rs, asc of HVT, LVt reached a higher level of lung volume (2.0 versus 1.5 L). Best PEEP was higher in LVT than in HVT (12.3 ± 2.0 versus 6.6 ± 1.6 cmH2O, p < 0.05). Best PEEP in the descending phase was higher than in the ascending phase for both LVT and HVT. Conclusion: HVT can cause tidal recruitment which is responsible for the higher Cst, rs and the lower W, rs, asc, however, the Lvt reached a higher lung recruitment at the same pressure limit, influencing the calculation of the best PEEP. After a high pressure recruiting maneuver a given PEEP value could achieve a higher EELV.

A previously reported empirical equation fitted animal and human PV data extremely well. In that equation, the function: F = (1 + e(c-P)/d), approximates the integral of a normal distribution and could represent the progressive recruitment or de-recruitment of alveoli with normally distributed opening or closing pressures, respectively. We multiplied such a "fractional recruitment" function by the classic exponential "elastic function" yielding: V = b (1-ekP)/ (1 + e(c-P)/d), where b, k, c, and d correspond to vital capacity, elastic coefficient, mean opening or closing pressure, and a distribution width (proportional to the standard deviation), respectively. We fitted inspiratory and expiratory PV curves from eight ARDS patients obtained with the super-syringe method up to pressures of 55 cmH2O. The new equation fitted the data with high accuracy (R2 = 0.9996) yielding an average mean closing pressure "c" that was 7 cmH2O lower than the mean opening pressure. The values of deflation "k" were all within the normal range, thus supporting the "baby lung" concept in ARDS.

EFFECTS OF FUROSEMIDE IN RESPIRATORY MUCUS PROPERTIES AND TRANSPORTABILITY IN PATIENTS UNDER MECHANICAL VENTILATION. Kondo CS, Macchione M, Guimarães ET, Carvalho CRR, King M, Saldiva PHN, Lorenzi-Filho G. Pulmonary Division and Department of Pathology, School of Medicine, University of São Paulo and Federal University of São Paulo, SP, Brazil and Pulmonary Research Group, University of Alberta, Edmonton, Canada.

The use of IV furosemide is common practice in patients under mechanical ventilation (MV), however its effects on the respiratory mucus are largely unknown. Furosemide can affect the respiratory mucus either directly through inhibition of NaK(Cl)2 co-transporter on the basolateral surface of airway epithelium or indirectly through increased diuresis and patient's dehydration. We investigated the mucus physical properties and transportability of mucus obtained from 27 patients under MV distributed in 2 groups, furosemide (10-200 mg IV) (n = 12) and control (n = 15). Mucus was collected at time 0, 1, 2, 3 and 4 hours. Mucus was studied by means of a micrortheometer, in vitro mucus transport (MT) (frog palate), contact angle (CA) and cough clearance (CC) (simulated cough machine). MT remained constant in the control group and decreased significantly in the furosemide group 1.01 ± 0.21, 0.81 ± 0.16*, 0.77 ± 0.20*, 0.82 ± 0.22* and 0.82 ± 0.20* at time 0, 1, 2, 3 and 4 hs, respectively (*p < 0.001, different from 0). The remaining parameters did not change significantly in both groups. We conclude that IV furosemide can acutely impair MT in patients under MV.

Background: Pressure support ventilation (PSV) is a ventilatory mode which theoretically permits a total control of inspiratory time (Ti) by the patients. But, Ti is strongly dependent on peak flow, ventilator end inspiratory criteria, patient respiratory drive, and initial flow rate (pressure slope). Objective: analyze the flow pattern at different flow rates with normal and high airway resistance. Methods: we studied 3 normal male subjects under PSV by a facial mask delivered by a Evita 2 ventilator (Dräger, Lubeck  Germany) that allows a fine set of initial flow rate. The pressure (PS) was preset to achieve a tidal volume (VT) of nearly 10 mL/kg (mean 8 cmH2O) at zero PEEP with a FiO2 enough to maintain a SatO2 above 96% (mean 0.3). The flow rate was changed from 0.064 s to 0.75 s and 1.5 s. Then, a external resistance of 20 cmH2O/l/s was connected to the airways. The following variables were recorded and analyzed: Ti, inspiratory peak flow (PF), time to achieve peak flow (TPF) and VT. Results: the PF and TPF changed significantly with flow rates (p = 0.04 and p < 0.001, respectively) at the normal resistance procedure. At the high resistance, only the TPF changed significantly (p < 0.001). Both VT and Ti did not vary in the two procedures.

Conclusion: The VT and Ti remained unchanged with different flow rates and normal and high resistance. These findings suggested that VT and Ti could be the most important determinants of flow pattern in normal subjects under PSV in different slopes and inspiratory resistance conditions.

Background: the presence of intrinsic PEEP (PEEPi) has major implications on the respiratory mechanics of patients with obstructive airway disease. We do not know any model of PEEPi simulator that allows the study of PEEPi and its ventilatory mechanics effects in healthy humans. Objective: evaluate the ventilatory mechanics changes with an original PEEPi simulator. Material and Method: we developed a PEEPi simulator using a facial mask connected to a Y circuit where a compressive latex tube in a water column was added to the expiratory limb (positive pressure in circuit = PEEP) and an unidirectional valve to the inspiratory lim, in order to allow the start of the inspiratory flow only after the pressure in the mask becomes lower than the ambient pressure. In this system we named the pressure at the mask and at the circuit as "alveolar" pressure ("Palv"); and the pressure proximal to the unidirectional valve as "airway" pressure ("Paw"). We studied 5 healthy volunteers under spontaneous ventilation. The ventilatory mechanics were obtained at basal conditions (no PEEPi); with PEEPi = 10 cmH2O; with PEEPi = 10 cmH2O and progressive CPAP levels to increase the "Paw". The analyzed parameters were: 1) work of breathing, showed as the relation between work obtained in each step and work in the basal condition (Wob%); 2) "Palv" variation ("Palv") showed as the necessary pressure variation in the circuit to allow the beginning of the inspiratory flow. Results: the presence of PEEPi resulted in an increase in W% and "Palv". The use of CPAP was effective in attenuate the W% and "Palv" due to PEEPi  Figure. Conclusions: the simulator was effective in the study of ventilatory mechanics pattern due to the presence of PEEPi.

Background: the ability of VAPSV and VS to assure a preset VT and decrease the work of breathing during noninvasive positive pressure ventilation (NPPV) is not well known. Objective: evaluate the ventilatory mechanics of VAPSV and VS, also comparing with volume assist-control (Vac), during NPPV. Material and Method: we used a stimulator of respiratory system consisted of a head model where a pneumatic face mask was fitted. The head airway was connected to a mechanical lung model. Different conditions of compliance (C), resistant (R) and inspiratory efforts (E-L/min) were simulated and ventilated by the studied modes. The ventilators were used as following: BIRD 8400® Vac  VT 740 ml, inspiratory square flow (IF) IL/s VAPSV  VT 740 ml, IF IL/s, PS cmH2O. Servo 300® VS  VT 740 ml, rise time 5%. The analyzed parameters were: 1) inspiratory work of breathing (Winsp%) showed as the relation between Winsp obtained in each simulation and Winsp of Vac in the basal condition (C = 85; R = 5; E = 60); 2) VT% showed as the relation between the VT achieved in the lung model circuit and the preset inspiratory ventilator VT; 3) acceleration flow time (Ta  ms) defined as the time spend to achieved inspiratory flow of 1 L/s. Results: Winsp% was smaller in VAPSV than in Vac and VS (p = 0.05 and p < 0.001) and VT% was similar in the three modes  Figure. Ta was similar in Vac and VAPSV in all simulated conditions (45 to 50 ms) and smaller than VS (70 ms  E120 to 220 ms  R15). Significant variations in VT (348 to 720 ml) were observed during the use of VS in high) impedance simulation (C30). Conclusion: the global performance of VAPSV is superior to VS in experimental conditions of NPPV.

Lung recruitment in ARDS occurs at peak inspiratory pressures. We compared the effectiveness of the two maneuvers designed to maximally recruit the lung. Method: saline lavage injured sheep were randomly assigned to 3 groups: CPAP 40 cmH2O for 1 min (CPAP40) (n = 3) pressure controlled ventilation 20 cmH2O with PEEP 40 cmH2O for 2 min (PCV60) (n = 3) and no RM (control) (n = 3). After each RM animals were ventilated with PCV, rate 20/min, I:E 1:1, peak airway pressure 35 cmH2O and PEEP 20 cmH2O for 30 min. Animals were then disconnected from the ventilator for 30 seconds followed by another RM and 30 min ventilation. Each RM was repeated 4 times. Results: all animals survived the study period. Oxygenation improved significantly (p < 0.05) in the PCV60 group after the second RM. There was a nonsignificant tendency for further recruitment with additional Rms. Lung tissue is being histologically evaluated for extent of lung injury.

We conclude that morphometric analysis is a good method for detecting pulmonary lesions in acute lung injury induced by oleic acid as early as 4 hours after infusion of OA. Mannitol infusion partially prevents this acute lung injury.

In order to evaluate the alterations in ECM in the acute respiratory distress syndrome, 37 ARDS patients, mean age 46 ± 13 years old, were retrospectively studied and divided in groups according to the phase (early or late disease) and to the etiologic of ARDS: pulmonary (i.e., pneumonia) or extra-pulmonary (i.e., sepsis, extracorporeal circulation). Using the image analysis, the collagen and elastic fibers content of the alveolar septum were quantified in autopsied lung samples, stained by the picrossirius and the oxidated resorcin fucsin methods respectively. In addition, values of dynamic compliance of the respiratory system at the day of death were retrospectively accessed. Data were analyzed by ANOVA, setting the significance in 5%. In the early phase of ARDS collagen fibers content was significantly higher in the pulmonary group, no differences were observed in fibers content in the late phase of the disease between groups. Codyn was always higher in extra-pulmonary ARDS in the early and late phases. We conclude that pulmonary remodeling in ARDS seems to be influenced by the initial site of injury (pulmonary or extra-pulmonary) and mechanical properties of lung parenchyma may be influenced by the differences.

Introduction: Cardiopulmonary bypass (CPB) is a well known factor that potentially decreases exposure of blood to non-endotelial surfaces, ischemia/reperfusion of organs, protamine reactions and others. The lung, by its physiological particularities, is one of the main organs affected by the capillary leak syndrome, leading to oxygenation and mechanics changes. This study aims to investigate the immediate alterations in lung function after CPB in adult patients during cardiac surgeries. Method: Twenty four patients of both sexes (age: 36-82 y; weight: 56-92 kg) were studied before and after CPB. General anesthesia was induced and maintained with fentanyl, midazolan and low concentration of isoflurane. Respiratory monitoring was achieved by means of intermittent measurements of arterial blood gases and continuous evaluation of PETCO2, inspired fraction of oxygen (FIO2) and expired tidal volumes (VT) flows, pressures, static compliance (Cst) and resistance (Raw) by a solid state/single beam nondispersal infrared unit main stream capnography with fixed orifice differential pressure pneumotach (CO2SMPLUS-Novametrics). Data were gathered before and after CPB, and analyzed by Kolmogorov-Smirnov test, modified by Lilliefors. Comparison between groups were performed by Student's t test and Mann-Whitney rank sum test. Significance was set at 5%. Results: CPB time varied from 60 to 185 min (mean = 108.3). Data base CPB was PaO2/FIO2 417.52 ± 124.15. Cst 52.04 ± 18.43 and raw of 12.25 ± 5.95. After CPB the PaO2/FIO2 was 320.08 ± 100.71; Cst 49.21 ± 17.07 and raw of 12.08 ± 5.29. Conclusion: in patients with the same respiratory pattern, considering both pre and post CPB, we found a significant decrease in oxygenation parameters, not followed by significant changes in lung mechanics as would be expected.